Lersivirine (UK-453061)

Lersivirine (UK-453061) is a potent and selective inhibitor of nonnucleoside reverse transcriptase (NNRTI) with IC50 of 0.119 μM.

Product information

CAS Number: 473921-12-9

Molecular Weight: 310.35

Formula: C17H18N4O2

Chemical Name: 5-((3,5-diethyl-1-(2-hydroxyethyl)-1H-pyrazol-4-yl)oxy)isophthalonitrile

Smiles: CCC1=NN(CCO)C(CC)=C1OC1C=C(C=C(C=1)C#N)C#N

InChiKey: MCPUZZJBAHRIPO-UHFFFAOYSA-N

InChi: InChI=1S/C17H18N4O2/c1-3-15-17(16(4-2)21(20-15)5-6-22)23-14-8-12(10-18)7-13(9-14)11-19/h7-9,22H,3-6H2,1-2H3

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO 62 mg/mL (199.77 mM) Ethanol 62 mg/mL (199.77 mM)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

Lersivirine binds to HIV-1 wt reverse transcriptase (RT) with Kd of 624 nM. Lersivirine is a very weak inhibitor of human DNA polymerase beta, with an extrapolated geometric mean IC50 of approximately 20 mM resulting in a predicted selectivity index of 166, 000. Lersivirine is able to inhibit HIV-1 virus replication in MT-2 cells infected with wt NL4-3, with an EC50 ranging from 5 nM to 35 nM against an MOI ranging from 0.005 to 0.5. Lersivirine retains activity against 80% of viruses with genotypes containing K103N as a single NNRTI mutation (versus 7% for efavirenz), 57% of viruses with genotypes containing Y181C as a single NNRTI mutation (43% for efavirenz), and 46% of viruses with genotypes containing G190A as a single NNRTI mutation (0% for efavirenz). Lersivirine inhibits the replication of strain Ba-L in PBL, with a geometric mean EC50 equal to 3.38 nM (95% CI, 2.26 to 5.05 nM) and an EC90 equal to 9.87 nM (95% CI, 6.63 to 14.7 nM), with no cytotoxicity observed up to 50 μM. Combinations of lersivirine with drugs of the NRTI class (abacavir, didanosine, emtricitabine, lamivudine, tenofovir, and zidovudine) results in synergistic interactions.

In Vivo:

Lersivirine is not teratogenic in mice.

References:

1. Corbau R, et al. Antimicrob Agents Chemother, 2010, 54(10), 4451-4463.
2. Charles E Mowbray, et al. Bioorg Med Chem Lett. 2009 Oct 15;19(20):5857-60.
3. Gregg D Cappon, et al. Birth Defects Res B Dev Reprod Toxic

Products are for research use only. Not for human use.